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Review
. 2025 Apr 18;14(8):2810.
doi: 10.3390/jcm14082810.

Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice

Bogdan Marian Sorohan  1   2 , Dorina Tacu  2 , Constantin Gîngu  1   2 , Silviu Guler-Margaritis  1   2 , Bogdan Obrișcă  1   3 , Maria-Daniela Tănăsescu  1   4 , Gener Ismail  1   3 , Cătălin Baston  1   2
Affiliations
Review

Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice

Bogdan Marian Sorohan et al. J Clin Med. .

Abstract

Antibody-mediated rejection (AMR) is a leading cause of kidney graft failure. Complement activation is involved in the AMR process. Our aim is to provide the current understanding of the pathophysiology related to complement-mediated injury in AMR, to present the current evidence regarding complement blockade in AMR management, and to point out emerging therapies and future directions in this area. The complement system plays an important role in the onset and progression of AMR. There is a balance between complement-dependent and -independent mechanisms in the development of rejection lesions. Classic and leptin pathways are involved in this process. C4d positivity is no longer a mandatory feature for AMR diagnosis but remains an independent predictor of negative outcomes. The current evidence regarding AMR treatment is limited. Terminal and proximal complement blockade has gained recognition in clinical practice. Eculizumab and C1 inhibitors are effective in the treatment of AMR as adjuvant therapies to the standard of care. The availability of novel complement inhibitors will lead to more effective and tailored treatment strategies.

Keywords: antibody; complement; kidney; pathophysiology; rejection; transplant; treatment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Classical and lectin complement pathways activation in AMRs (HLAs—human leukocyte antibodies; DSAs—donor-specific antibodies; DAMPs—damage-associated molecular patterns; MASP—mannan-binding lectin serine protease; PRR—pattern recognition receptor; MBL—mannose-binding lectin; MAC—membrane attack complex).
See this image and copyright information in PMC

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